New methods for the possible presence DNA specific for Aspergillus or Trichosporon species were developed. In aspergillus PCR, Aspergillus 18S rRNA encoding gene was amplified from five strains of Aspergillus species by the nested PCR but not from other microorganisms. Results of preliminary investigation of this method demonstrated efficient detections of Aspergillus species in serum samples of rats model of aspergillosis and 29 patients with invasive aspergillosis. In trichosporon PCR, Trichosporon 26S rRNA encoding gene was amplified from two strains of Trichosporon species, and detected by the nested PCR in 64% of serum samples of patients with trichosporonosis, while glucuronoxylomannan antigen was detected in 55% of samples. The high sensitivity and specificity of the nested PCR indicate that the assay can provide early diagnosis with sufficient accuracy to be clinically useful for patients with opportunistic fungal infection.

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The deep-seated mycosis occurred in immunocompromized patients. Normally, the deep-seated mycosis became sever infection because of the defects of host defense or the adverse effects of antifungal agents. The major factors of the reason on the severity of the deep-seated mycosis depends on the pathogenesity and the drug resistance for antifungal agents in infected fungi. The clinical factors related with hosts defenses are important to the other reason on the severity. We investigated that the multiple drug resistant (MDR) mechanism may be one of the major roles plays in the azole resistant Candida albicans strains isolated form the patients with oropharyngeal candidiasis infected HIV. We analyzed which clinical factors are related with the prognosis of the patients with pulmonary cryptococcosis and aspergilloma. The titer of cryptococcal capsular antigen was earlier improve in the patient without underline disease than in the patients with underline diseases diagnosed pulmonary cryptococcosis. CRP was higher in the death cases in the patients with pulmonary aspergilloma, compared with alive cases.

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Recently, deep seated fungal infection is one of important and common complication of immunocompromised patients and is often intractable. The key of the management of patients with high risks of these infection is understanding the patients' condition and make effort to prevent propression of the disease by the prediction of the break out. Active and logical treatments are also needed to control the infection.

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In surgery, deep-seated fungal infection is not rare. In our institute, fungal infection was analyzed during postoperative periods. As pathogen, fungus was the second frequent pathogen after the operations for esophageal cancer and gastric cancer, and the third pathogen after hepatobiliopancreatic cancer and colon cancer. Furthermore, fungus was found more frequently pathogen from distant infection than that from local foci.
Especially in CV catheter sepsis, fungus was main pathogen (60%). In order to inhibit CV catheter sepsis, nutrition support team (NST) has been induced in our institute for prevention of external pathway of fungus. After NST, the frequency of CV catheter sepsis decreased from 12% to 3.6%, and the isolated frequency of fungus in catheter sepsis patients also decreased from 84% to 16%, respectively. It demonstrates that the activity of NST successfully prevents the external pathway of fungus in CV catheter indwelling patients. However, internal pathway (fungal translocation) still remains, and that issue has to be overcome.
Molecular biological technique was applied for diagnosis of fungemia. PCR-RFLPs was performed by using specific primer of 18s rRNA in V4 region. Clinical samples were applied for PCR-RFLPs, and antifungal therapy was performed according as the results of PCR-RFLPs. It indicated that molecular biological technique was useful for diagnosis of fungemia.

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Ophthalmological mycosis were seen as blephlitis, conjunctivitis, keratitis, orbititis, endophthalmitis. These dideases were almost hard to diagnose and were rare and refractory to treatment. Among them, keratomycosis was most frequent and relatively refractory to treatment. Orbit mycosis was rare but most refractory to treatment. Almost of them were fatal in our knowledge.

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Approximately 15% of non-pregnant women and 30% of pregnant women yield positive cultures of Candida species in the vaginal specimens. A diagnosis of vulvovaginal candidiasis (VVC) should only be made when Candida spp. are isolated from the vulvovaginal area, together with the presence of signs and symptoms. In Japan several topical drugs for vaginal candidiasis are available, but oral azoles has not been approved. According to our studies, treatment with topical drugs resulted in symptomatic cure and negative culture conversion in 80%-90% of patients at the end of initial treatment (6-14 days or high-dose one day treatment according to the drug used). However Candida spp. reappeared in the vagina after several weeks in 7-34% (according to the drug used) of initially cured cases, and some of them were again symptomatic. A small proportion of women experienced three or more episodes of symptomatic VVC annually. Repeated reinfection from a gastrointestinal reservoir or sexual transmission, subclinical presence of yeasts in the vagina, impaired host defense mechanisms, enhanced Candida virulence have been discussed as factors relating to recurrent vulvovaginal candidiasis (RVVC). Oral ketoconazole give the best result in treating RVVC, however it is not used because of possible side effects. Several studies have evaluated oral therapy for RVVC with fluconazole and itraconazole that have less side effects. However, several reports have documented the emergence of fluconazole-resistant candidiasis in long-term treatment of mycotic diseases other than VVC. The optimal treatment for RVVC remains difficult to establish.

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Dermatomycoses are a common category of fungal infections affecting the skin and subcutaneous tissues. Recent advances in topical and systemic antifungal chemotherapy have provided us with satisfactory results in most of the superficial fungal infections both clinically and mycologically. Despite the efficacy of antifungal agents, however, there are dermatomycoses that do not respond to our current standard regimens of treatment. Factors concerning the treatment-resistance, such as host's underlying conditions and fungal virulence, are discussed in detail.

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Human immunodeficiency virus (HIV) infection is unique among the cutaneous fungal infections caused by defects of the cell-mediated immune system. A complex interplay exists in the host between fungal virulence factors favoring disease, and immune and non-immune host mechanisms defending against disease. Cell-mediated immunity appears of paramount importance in defense against histoplasmosis, cryptococcosis, mucocutaneous candidiasis, and dermatophytosis.
Mucocutaneous candidiasis is especially common in patients with HIV infection. Anti-fungal medicines were effective against candidiasis. However, anti-fungal medicine-resistant candida has been observed. Anti-fungal ointment was effective against dermatophytosis and seborrheic dermatitis. No cases of cutaneous fungal infection resistant to anti-fungal medicine have been observed.

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A patient with myelofibrosis complicated by recurrent candidemia died despite treatment with amphotericin B and fluconazole. Autopsy revealed systemic candidiasis with fungal verrucae in the right ventricle and the root of the pulmonary artery. The strains of Candida albicans isolated from the blood had become resistant to amphotericin B and fluconazole during therapy, as well as to other azole antifungals that had not been used. Pulsed-field gel electrophoresis showed that the resistant isolates had the same genotype as the sensitive strains isolated before treatment, but a chromosomal change in >2.0 Mb-bands was observed after treatment. It was thus proved that these repeatedly isolated C. albicans strains which were causing the continued fungemia in our patient were all the same strain and were acquiring resistance to antifungal agents during the therapy.

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